1. Field of the Invention
The present invention relates to a device for use in a random access, isolation fluid-based, analytical instrument. More particularly, the invention is directed to a wash cup for use with such instrument whereby fresh water, test sample, and isolation fluid, all of which being necessary for the operation of the instrument, can be introduced therein.
Prior art devices which are presently in use with systems such as that described above suffer from an inherent disadvantage. The isolation fluid normally used in such devices is a fluorinated oil having a specific gravity significantly greater than water. Accordingly, segments of the fluid settle to the bottom of the sampling device or wash cup, and disrupt the water level regulating activity of the cup. The present invention completely overcomes this serious difficulty representative of the prior art.
2. Present State of the Art
The present invention relates to, and is directly usable in conjunction with, a random access, isolation fluid-based analytical instrument. In such systems, conduits are used, the inner walls of which are coated with immiscible liquid, such as a fluorinated oil. In use, the reagent to be utilized in a particular assay and/or the test sample to be assayed proceeds past one or more detection stations which, for example, can comprise a spectrophotometer or colorimeter, and discrete quantities of the test sample and/or reagents may be separated by air or other separating fluid. In order to avoid such inadvertent mixing of the discrete liquid samples, the walls of the conduit are coated with an immiscible liquid such as is described in the Smythe, et al., U.S. Pat. No. 3,479,141, assigned to the instant assignee. The Smythe, et al patent discloses a transport system for an automatic analysis apparatus in which a series of aqueous liquid samples are processed as a flowing fluid stream with substantially no contamination between the flowing liquid segments. A fluoropolymer conduit, such as TEFLON.RTM. polymer, and intersample carrier segments of silicone are employed. Smythe, et al. teach that the silicone encapsulates aqueous liquid segments, substantially completely eliminating the intermixing of successive liquid segments. Reagents are separately introduced on a continual basis, such as in conventional fashion as described with respect to previous continuous-flow systems.
In Smythe, et al., U.S. Pat. No. 4,253,846, also assigned to the instant assignee, selective injection of reagent into a moving stream of sample segments is provided to such a continuous flow system, and allows for an increase in the efficiency and throughput of sample processing. Using injectors such as poppet valves, the reagent is introduced by piercing the immiscible liquid layer encapsulating the selected sample segments. The immiscible liquid layer reforms after injection to maintain sample integrity and prevent carryover to other samples in the system. Air and sample are alternately aspirated via a probe which periodically dips into a sample cup. The immiscible liquid is said to be introduced to the inlet end of the probe by an applicator (not shown) and aspirated along with air between successive sample immersions. The immiscible liquid can be a fluorocarbon and both the conduit wall and the poppet valve tip can be a fluorinated polymer. This patent does not further address the actual mechanism of immiscible liquid introduction and clearly indicates that it is separate from the "on-line" introduction of reagent.
Diebler, et al., U.S. Pat. No. 4,121,466, also assigned to the instant assignee, disclose a metering apparatus useful to either dispense or aspirate sample. The surface of the aspirating probe is coated with an immiscible liquid film which, in the preferred embodiment, is flowed continuously down the peripheral probe surface at a rate substantially equal to the aspiration rate, so as to be eventually aspirated into the probe inlet. During immersion, excess immiscible liquid on the peripheral probe surface floats onto the surface of the liquid being aspirated but a small film remains on the probe surface. Also, during aspiration, a thin film of immiscible liquid continuously wets the interior probe surface. As the probe is withdrawn, the flow of immiscible liquid is commenced so as to be aspirated along the probe immediately upon withdrawal thereof from the liquid. Segments of the immiscible liquid and aspirated liquid are therefore successively passed along the probe system.
Smythe, et al., U.S. Pat. No. 4,259,291, also assigned to the instant assignee, refers to the continuous flow systems described in the above Smythe, et al '291 and Diebler, et al '466 patents and addresses the need for more precise and uniform application of protective immiscible liquid coatings. An applicator directly surrounds the probe and layers a thin uniform film of immiscible liquid on the outer surface thereof. The applicator is moved relative to the probe to coat its outer surface. An aspirating mechanism connected to the probe alternately aspirates controlled volumes of air and aqueous sample therethrough. Immiscible liquid is said to be drawn into the probe along with the air segments so aspirated. Thus, alternating sample and air segments encased within the immiscible liquid are passed along the probe to a rotary valve which transfers each aspirated aqueous sample in turn from the probe to a conduit for dispensing to an analytical system. As described herein, a pool of wiped immiscible liquid forms about the probe due to the interplay of surface forces of the liquid in combination with the wetting forces of the immiscible liquid with respect to the probe surface. When the probe is withdrawn from the sample cup, this pool forms a small globule of immiscible liquid over the inlet of the probe, inasmuch as it preferentially wets the probe material to the substantial exclusion of the aqueous sample. This patent teaches that the globule of immiscible liquid is aspirated into the probe inlet along with an air segment. Reagent is introduced "downstream" in a manner which is not further described.
Each of the above patents has provided an advance of one sort or another in the elimination of successive sample intermixing and carryover. This end has been widely recognized as a major consideration in the improvement of continuous flow systems. The combined references provide a significant background literature on the technology available to prevent interaction of segments in continuous flow analysis systems, and the disclosure of the references are hereby incorporated herein by reference thereto.
Other aspects of the state of the art which are pertinent to the present invention include two continuous flow assay instruments currently marketed by the assignee herein, Technicon Instruments Corporation, namely the Simultaneous Multichannel Analyzer"(SMA.RTM.) and the Simultaneous Multichanneled Analyzer with Computer (SMAC.RTM.). Both of these instruments utilize a mechanized probe for transferring a test sample and the reagent liquids into the flowing stream. However, in order to minimize cross-contamination between successive samples, it is necessary to wash the probe. Accordingly, a washing cup is utilized with these instruments. Thus, the washing cup serves (a) to remove remnants of prior samples taken by the probe, i.e., (b) to clean the probe, (c) to inject successive aqueous samples into the flowing stream, (d) to assure a continuous flow of fresh water through the cup, and (e) to assure that the liquid level remains relatively constant, thereby providing a relatively constant volume of fresh water for the instrument.